CFSA: Comparative flux sampling analysis as a guide for strain design

Genome-scale metabolic models of microbial metabolism have extensively been used to guide the design of microbial cell factories, still, many of the available strain design algorithms often fail to produce a reduced list of targets for improved performance that can be implemented and validated in a...

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Main Authors: R.P. van Rosmalen, S. Moreno-Paz, Z.E. Duman-Özdamar, M. Suarez-Diez
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Metabolic Engineering Communications
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Online Access:http://www.sciencedirect.com/science/article/pii/S2214030124000130
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author R.P. van Rosmalen
S. Moreno-Paz
Z.E. Duman-Özdamar
M. Suarez-Diez
author_facet R.P. van Rosmalen
S. Moreno-Paz
Z.E. Duman-Özdamar
M. Suarez-Diez
author_sort R.P. van Rosmalen
collection DOAJ
description Genome-scale metabolic models of microbial metabolism have extensively been used to guide the design of microbial cell factories, still, many of the available strain design algorithms often fail to produce a reduced list of targets for improved performance that can be implemented and validated in a step-wise manner. We present Comparative Flux Sampling Analysis (CFSA), a strain design method based on the extensive comparison of complete metabolic spaces corresponding to maximal or near-maximal growth and production phenotypes. The comparison is complemented by statistical analysis to identify reactions with altered flux that are suggested as targets for genetic interventions including up-regulations, down-regulations and gene deletions. We applied CFSA to the production of lipids by Cutaneotrichosporon oleaginosus and naringenin by Saccharomyces cerevisiae identifying engineering targets in agreement with previous studies as well as new interventions. CFSA is an easy-to-use, robust method that suggests potential metabolic engineering targets for growth-uncoupled production that can be applied to the design of microbial cell factories.
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institution Kabale University
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publisher Elsevier
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series Metabolic Engineering Communications
spelling doaj-art-27751fbd27aa4962a865fd9ac60294b52024-12-17T04:59:36ZengElsevierMetabolic Engineering Communications2214-03012024-12-0119e00244CFSA: Comparative flux sampling analysis as a guide for strain designR.P. van Rosmalen0S. Moreno-Paz1Z.E. Duman-Özdamar2M. Suarez-Diez3Laboratory of Systems and Synthetic Biology, Stippeneng 4 6708 WE Wageningen, the NetherlandsLaboratory of Systems and Synthetic Biology, Stippeneng 4 6708 WE Wageningen, the NetherlandsLaboratory of Systems and Synthetic Biology, Stippeneng 4 6708 WE Wageningen, the NetherlandsCorresponding author.; Laboratory of Systems and Synthetic Biology, Stippeneng 4 6708 WE Wageningen, the NetherlandsGenome-scale metabolic models of microbial metabolism have extensively been used to guide the design of microbial cell factories, still, many of the available strain design algorithms often fail to produce a reduced list of targets for improved performance that can be implemented and validated in a step-wise manner. We present Comparative Flux Sampling Analysis (CFSA), a strain design method based on the extensive comparison of complete metabolic spaces corresponding to maximal or near-maximal growth and production phenotypes. The comparison is complemented by statistical analysis to identify reactions with altered flux that are suggested as targets for genetic interventions including up-regulations, down-regulations and gene deletions. We applied CFSA to the production of lipids by Cutaneotrichosporon oleaginosus and naringenin by Saccharomyces cerevisiae identifying engineering targets in agreement with previous studies as well as new interventions. CFSA is an easy-to-use, robust method that suggests potential metabolic engineering targets for growth-uncoupled production that can be applied to the design of microbial cell factories.http://www.sciencedirect.com/science/article/pii/S2214030124000130Metabolic engineeringGenome scale metabolic modellingFlux sampling
spellingShingle R.P. van Rosmalen
S. Moreno-Paz
Z.E. Duman-Özdamar
M. Suarez-Diez
CFSA: Comparative flux sampling analysis as a guide for strain design
Metabolic Engineering Communications
Metabolic engineering
Genome scale metabolic modelling
Flux sampling
title CFSA: Comparative flux sampling analysis as a guide for strain design
title_full CFSA: Comparative flux sampling analysis as a guide for strain design
title_fullStr CFSA: Comparative flux sampling analysis as a guide for strain design
title_full_unstemmed CFSA: Comparative flux sampling analysis as a guide for strain design
title_short CFSA: Comparative flux sampling analysis as a guide for strain design
title_sort cfsa comparative flux sampling analysis as a guide for strain design
topic Metabolic engineering
Genome scale metabolic modelling
Flux sampling
url http://www.sciencedirect.com/science/article/pii/S2214030124000130
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AT msuarezdiez cfsacomparativefluxsamplinganalysisasaguideforstraindesign